Evaluation of 3-O-methyldopa as a biomarker for aromatic L-amino acid decarboxylase deficiency in 7 Brazilian cases

Aromatic L-amino acid decarboxylase (AADCD) deficiency is an autosomal recessive neurometabolic disorder, caused by biallelic mutations in the DDC gene, that impairs the synthesis or metabolism of neurotransmitters leading to severe motor dysfunction. The main clinical signs are oculogyric crisis, hypotonia, hypokinesia, and dystonia. The biochemical diagnosis can be performed in cerebrospinal fluid by neurotransmitter analysis, which requires an invasive lumbar puncture, and the sample needs to be shipped frozen to a reference laboratory, usually across a country border. Measurement of AADC activity in plasma is also possible, but available in a few labs globally. 3-O-methyldopa (3-OMD) is a catabolic product of L-dopa and it is elevated in patients with AADC deficiency. The quantification of 3-OMD can be performed in dried blood spots (DBS), a sample that could be shipped at room temperature. 3-OMD levels of AADCD patients and controls were quantified in DBS by liquid chromatography tandem mass spectrometry. DBS samples from 7 Brazilian patients previously diagnosed with AADCD were used to validate the 3-OMD quantification as a screening procedure for this condition. All AADCD patients had at least a four-fold increase of 3-OMD. Thus, 3-OMD seems to be a reliable marker for AADCD, with potential use also in the newborn screening of this disease

Epilepsy Profile in Infants with Congenital Zika Virus Infection

Submitted by Ana Beatriz Oliveira ([email protected]) on 2019-04-12T14:19:17Z No. of bitstreams: 1 Epilepsy Profile in Infants with Congenital Zika Virus Infection.pdf: 63897 bytes, checksum: ed83f2a2d64fe6b5621f5c5d292771e5 (MD5)Approved for entry into archive by Ana Beatriz Oliveira ([email protected]) on 2019-04-12T14:28:28Z (GMT) No. of bitstreams: 1 Epilepsy Profile in Infants with Congenital Zika Virus Infection.pdf: 63897 bytes, checksum: ed83f2a2d64fe6b5621f5c5d292771e5 (MD5)Made available in DSpace on 2019-04-12T14:28:28Z (GMT). No. of bitstreams: 1 Epilepsy Profile in Infants with Congenital Zika Virus Infection.pdf: 63897 bytes, checksum: ed83f2a2d64fe6b5621f5c5d292771e5 (MD5) Previous issue date: 2018Dr. Henrique Santillo Rehabilitation and Readaptation Center. Goiânia, Brazil.Oswaldo Cruz University Hospital. Recife, Brazil.Association for Assistance of Disabled Children. Recife, Brazil.Oswaldo Cruz University Hospital. Recife, Brazil.Hospital Infantil Albert Sabin. Fortaleza, Brazil.Dr. Henrique Santillo Rehabilitation and Readaptation Center. Goiânia, Brazil.Fundação Oswaldo Cruz. Instituo Aggeu Magalhães. Recife, PE, Brasil.Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. São Paulo, Brazi

Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies

ABSTRACT Congenital Zika syndrome is an emergent cause of a congenital infectious disorder, resulting in severe damage to the central nervous system and microcephaly. Despite advances in understanding the pathophysiology of the disease, we still do not know all the mechanisms enrolled in the vertical transmission of the virus. As has already been reported in other types of congenital infectious disorders in dizygotic twin pregnancies, it is possible that the virus affects only one of the fetuses. In this article, we report on two cases of twin pregnancies exposed to the Zika virus, but with only one of the fetuses affected with microcephaly and brain damage. This indicates the urgent need for more studies regarding the pathophysiology of viral infection and the mechanisms involved in the natural protection against the virus

Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients

Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects.

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment